POS1222 FOLIC ACID AND METHOTREXATE USE AND THEIR ASSOCIATION WITH COVID-19 DIAGNOSIS AND MORTALITY: AN ANALYSIS FROM THE UK BIOBANK
Authors: R. Topless, R. Green, S. Morgan, P. Robinson, T. Merriman, A. Gaffo
Journal: Annals of the Rheumatic Diseases (2022)

Background Folate metabolism is implicated in SARS-CoV-2 infectivity (Ref). Objectives To determine if methotrexate (an antifolate) or folic acid prescription were associated with a lowered and increased risk, respectively, for COVID-19 diagnosis or mortality in a large population-based cohort (UK Biobank). Methods Data from 380,380 UK Biobank participants with general practice prescription data were used. Criteria for COVID-19 diagnosis were 1) a positive SARS-CoV-2 test and / or 2) ICD-10 code for confirmed COVID-19 (U07.1) or probable COVID-19 (U07.2) in hospital records, or death records. This definition identified 26,003 individuals diagnosed with COVID-19 of whom 820 were known to have died from COVID-19. Logistic regression statistical models were adjusted for age group (4 categories), sex, ethnicity, Townsend deprivation index, BMI, smoking status, presence of rheumatoid arthritis, sickle cell disease, use of anticonvulsants, statins and iron supplements. Results Compared with people prescribed neither folic acid nor methotrexate, people prescribed folic acid supplementation had increased risk of diagnosis of COVID-19 (OR 1.51 [1.42; 1.61]). The prescription of methotrexate with or without folic acid was not associated with COVID-19 diagnosis (P≥0.18). Compared with people prescribed neither folic acid nor methotrexate, people prescribed folic acid supplementation had an increased risk of death after a diagnosis of COVID-19 (OR 2.64 [2.15; 3.24]) in a fully adjusted model. The prescription of methotrexate in combination with folic acid was not associated with an increased risk for death after a diagnosis of COVID-19 (1.07 [0.57; 1.98]). (Table 1) Table 1. COVID-19 diagnosis and associated death in people prescribed methotrexate and / or folic acid in the UKBB, compared to people not prescribed methotrexate or folic acid. Model 1 adjusted for age group, sex, ethnicity, Townsend deprivation index, BMI, smoking status Model 2 is model 1 plus adjustment by the presence of rheumatoid arthritis, sickle cell disease, use of statins, anticonvulsants and iron supplementation. Unadjusted Model 1 Model 2 OR[95% CI] P OR[95% CI] P OR[95% CI] P Neither Folic acid nor Methotrexate 1.0 - 1.0 - 1.0 - COVID-19 diagnosis Folic acid only 1.58[1.49; 1.68] &lt;0.001 1.60[1.50; 1.70] &lt;0.001 1.51[1.42; 1.61] &lt;0.001 Methotrexate and Folic acid 1.09[0.96; 1.23] 0.18 1.15[1.02; 1.30] 0.021 1.09[0.96; 1.23] 0.18 COVID-19 associated death Folic acid only 5.14 [4.23; 6.24] &lt;0.001 2.91 [2.38; 3.55] &lt;0.001 2.64[2.15; 3.24] &lt;0.001 Methotrexate and folic acid 1.47 [0.81; 2.67] 0.21 1.26 [0.70; 2.30] 0.44 1.07 [0.57; 1.98] 0.84 Conclusion We report increased risk for COVID-19 diagnosis and COVID-19-related death for people prescribed folic acid supplementation. The prescription and use of supplemental folic acid may confer risk of infection with the SARS-CoV-2 virus as well as the risk of death resulting from COVID-19. Our results also suggest that methotrexate might attenuate an increased risk for COVID-19 diagnosis and death conferred by folic acid. References [1]Zhang Y, Guo R, Kim SH, et al. SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication. Nature Communications 2021;12(1):1676. doi: 10.1038/s41467-021-21903-z Disclosure of Interests Ruth Topless: None declared, Ralph Green: None declared, Sarah Morgan: None declared, Philip Robinson Consultant of: Abbvie, Atom Biosciences, Eli Lilly, Gilead, Janssen, Novartis, UCB, Roche, Pfizer, Grant/research support from: Janssen, Novartis, Pfizer and UCB Pharma, Tony Merriman: None declared, Angelo Gaffo Consultant of: SOBI, Selecta